1. Field of the Invention
The present invention relates to a process for preparing an amine by cathodic reduction of a corresponding oxime derivative.
2. Description of the Background
Organic compounds having a plurality of chiral centers are frequently important building blocks and auxiliaries in the synthesis of other organic compounds in order to introduce the chiral centers mentioned or in order to build up a nonracemic stereocenter. Here, compounds which have a comparatively rigid skeleton and additionally comprise voluminous groups which can exercise a directing action in the synthesis of other organic compounds are frequently chosen as auxiliaries.
Cyclic compounds from the “chiral pool” are frequently of interest here. Particular mention may be made of cyclic terpenoids.
An example of such a compound is 8-phenylmenthol which is used, for example, as auxiliary in the asymmetric Diels-Alder reaction (E. Corey, Angew. Chem. 114 (2002), 1724-1741; K. C. Nicolaou, Angew. Chem. 114 (2002), 1742-1773).
Here, the hydroxyl group of menthol serves as functional group to introduce the auxiliary into a molecule so that a prochiral center is converted into a chiral center in a subsequent chemical reaction under the directing action of the auxiliary. However, menthol which can be used, for example, as alcohol component of an ester is comparatively labile and is therefore not the agent of choice for every reaction.
There is therefore a need to provide an amine analogue of menthol, derivatives thereof or analogous chiral auxiliaries.
The amine analogue of menthol and 8-methylmenthol has been used, for example, by M. C. Schopohl et al., Angew. Chem. 115 (2003), 2724-2727, in order to study the enantiofacial differentiation of individual caffeine gas molecules.
To obtain amine analogues of menthol, M. C. Schopohl et al., Synthesis 17 (2003), 2689-2694, propose preparing the corresponding amine from (+)-pulegone. As first step of the synthesis, the ethylenic double bond is reacted with a Grignard reagent to introduce a radical in the 8 position. This makes derivatization in said 8 position possible. The reaction produces a chiral center on the ring carbon in the 4 position. The Grignard reaction is unable to distinguish between the R and S form, resulting in formation of an epimer mixture in the reaction. After conversion of the keto function into an oxime, the (4S) epimer can be obtained. In the subsequent Beauvault-Blanc reaction with sodium in toluene, the oxime function is converted into an amino function which is present in the transconfiguration relative to the alkyl radical in the 4 position.
This represents a critical step in the synthesis in order to obtain a configuration corresponding to that of menthol.
In contrast to the above-described reduction with sodium, in the heterogeneous reduction over transition metal catalysts, either no reaction takes place or the corresponding amine is accompanied by an equimolar amount of an epimeric amine which can be separated off only with difficulty.
However, a disadvantage of the above-described reaction is the use of sodium, which, in addition, is used in comparatively large amounts.